Abstract
Rationale
Recent findings have shown a complexly regulated 5-HT system as it is linked to different kinds of aggression.
Objective
We focus on (1) phasic and tonic changes of 5-HT and (2) state and trait of aggression, and emphasize the different receptor subtypes, their role in specific brain regions, feed-back regulation and modulation by other amines, acids and peptides.
Results
New pharmacological tools differentiate the first three 5-HT receptor families and their modulation by GABA, glutamate and CRF. Activation of 5-HT1A, 5-HT1B and 5-HT2A/2C receptors in mesocorticolimbic areas, reduce species-typical and other aggressive behaviors. In contrast, agonists at 5-HT1A and 5-HT1B receptors in the medial prefrontal cortex or septal area can increase aggressive behavior under specific conditions. Activation of serotonin transporters reduce mainly pathological aggression. Genetic analyses of aggressive individuals have identified several molecules that affect the 5-HT system directly (e.g., Tph2, 5-HT1B, 5-HT transporter, Pet1, MAOA) or indirectly (e.g., Neuropeptide Y, αCaMKII, NOS, BDNF). Dysfunction in genes for MAOA escalates pathological aggression in rodents and humans, particularly in interaction with specific experiences.
Conclusions
Feedback to autoreceptors of the 5-HT1 family and modulation via heteroreceptors are important in the expression of aggressive behavior. Tonic increase of the 5-HT2 family expression may cause escalated aggression, whereas the phasic increase of 5-HT2 receptors inhibits aggressive behaviors. Polymorphisms in the genes of 5-HT transporters or rate-limiting synthetic and metabolic enzymes of 5-HT modulate aggression, often requiring interaction with the rearing environment.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Adell A, Celada P, Artigas F (2001) The role of 5-HT1B receptors in the regulation of serotonin cell firing and release in the rat brain. J Neurochem 79:172–182
Adell A, Celada P, Abellan MT, Artigas F (2002) Origin and functional role of the extracellular serotonin in the midbrain raphe nuclei. Brain Res Rev 39:154–180
Aghajanian GK, Wang RY (1977) Habenular and other midbrain raphe afferents demonstrated by a modified retrograde tracing technique. Brain Res 122:229–242
Albers HE, Bamshad M (1998) Role of vasopressin and oxytocin in the control of social behavior in Syrian hamsters (Mesocricetus auratus). Prog Brain Res 119:395–408
Alenina N, Kikic D, Todiras M, Mosienko V, Qadri F, Plehm R, Boye P, Vilianovitch L, Sohr R, Tenner K, Hortnagl H, Bader M (2009) Growth retardation and altered autonomic control in mice lacking brain serotonin. Proc Natl Acad Sci USA 106:10332–10337
Alia-Klein N, Goldstein RZ, Kriplani A, Logan J, Tomasi D, Williams B, Telang F, Shumay E, Biegon A, Craig IW, Henn F, Wang GJ, Volkow ND, Fowler JS (2008) Brain monoamine oxidase a activity predicts trait aggression. J Neurosci 28:5099–5104
Alleva E, Cirulli F, Bianchi M, Bondiolotti GP, Chiarotti F, De Acetis L, Panerai AE (1998) Behavioural characterization of interleukin-6 overexpressing or deficient mice during agonistic encounters. Eur J Neurosci 10:3664–3672
Amat J, Tamblyn JP, Paul ED, Bland ST, Amat P, Foster AC, Watkins LR, Maier SF (2004) Microinjection of urocortin 2 into the dorsal raphe nucleus activates serotonergic neurons and increases extracellular serotonin in the basolateral amygdala. Neuroscience 129:509–519
Amat J, Baratta MV, Paul E, Bland ST, Watkins LR, Maier SF (2005) Medial prefrontal cortex determines how stressor controllability affects behavior and dorsal raphe nucleus. Nat Neurosci 8:365–371
Assal F, Alarcon M, Solomon EC, Masterman D, Geschwind DH, Cummings JL (2004) Association of the serotonin transporter and receptor gene polymorphisms in neuropsychiatric symptoms in Alzheimer disease. Arch Neurol 61:1249–1253
Baca-Garcia E, Vaquero C, Diaz-Sastre C, Garcia-Resa E, Saiz-Ruiz J, Fernandez-Piqueras J, de Leon J (2004) Lack of association between the serotonin transporter promoter gene polymorphism and impulsivity or aggressive behavior among suicide attempters and healthy volunteers. Psychiatry Res 126:99–106
Bannai M, Fish EW, Faccidomo S, Miczek KA (2007) Anti-aggressive effects of agonists at 5-HT1B receptors in the dorsal raphé nucleus of mice. Psychopharmacology 193:295–304
Barkan T, Peled A, Modai I, Weizman A, Rehavi M (2006) Characterization of the serotonin transporter in lymphocytes and platelets of schizophrenia patients treated with atypical or typical antipsychotics compared to healthy individuals. Eur Neuropsychopharmacol 16:429–436
Beck AT, Ward CA, Mendelsohn M, Mock J, Erbaugh J (1961) An inventory for measuring depression. Arch Gen Psychiatry 4:561–571
Behzadi G, Kalen P, Parvopassu F, Wiklund L (1990) Afferents to the median raphe nucleus of the rat: retrograde cholera toxin and wheat germ conjugated horseradish peroxidase tracing, and selective d-[3H]aspartate labelling of possible excitatory amino acid inputs. Neuroscience 37:77–100
Belin MF, Nanopoulos D, Didier M, Aguera M, Steinbusch H, Verhofstad A, Maitre M, Pujol JF (1983) Immunohistochemical evidence for the presence of γ-aminobutyric acid and serotonin in one nerve cell. A study on the raphe nuclei of the rat using antibodies to glutamate decarboxylase and serotonin. Brain Res 275:329–339
Bell R, Hobson H (1994) 5-HT1A receptor influences on rodent social and agonistic behavior: a review and empirical study. Neurosci Biobehav Rev 18:325–338
Belozertseva IV, Bespalov AY (1999) Effects of NMDA receptor channel blockade on aggression in isolated male mice. Aggress Behav 25:381–396
Benmansour S, Cecchi M, Morilak DA, Gerhardt GA, Javors MA, Gould GG, Frazer A (1999) Effects of chronic antidepressant treatments on serotonin transporter function, density, and mRNA level. J Neurosci 19:10494–10501
Bennett AJ, Lesch KP, Heils A, Long JC, Lorenz JG, Shoaf SE, Champoux M, Suomi SJ, Linnoila MV, Higley JD (2002) Early experience and serotonin transporter gene variation interact to influence primate CNS function. Mol Psychiatry 7:118–122
Berkowitz L (1993) Aggression. Its causes, consequences and control. McGraw–Hill, New York
Bernstein IS, Rose RM, Gordon TP (1974) Behavioral and environmental events influencing primate testosterone levels. J Hum Evol 3:517–525
Bjork JM, Moeller FG, Dougherty DM, Swann AC, Machado MA, Hanis CL (2002) Serotonin 2a receptor T102C polymorphism and impaired impulse control. Am J Med Genet 114:336–339
Blader JC (2006) Pharmacotherapy and postdischarge outcomes of child inpatients admitted for aggressive behavior. J Clin Psychopharmacol 26:419–425
Blanchard RJ, Blanchard CD (1977) Aggressive behavior in the rat. Behav Biol 21:197–224
Blanchard RJ, Hori K, Blanchard DC, Hall J (1987) Ethanol effects on aggression of rats selected for different levels of aggressiveness. Pharmacol Biochem Behav 27:641–644
Blanchard DC, Rodgers RJ, Hendrie CA, Hori K (1988) ‘Taming’ of wild rats (Rattus rattus) by 5HT1A agonists buspirone and gepirone. Pharmacol Biochem Behav 31:269–278
Blanchard RJ, Wall PM, Blanchard DC (2003) Problems in the study of rodent aggression. Horm Behav 44:161–170
Blier P, de Montigny C (1998) Possible serotonergic mechanisms underlying the antidepressant and anti-obsessive-compulsive disorder responses. Biol Psychiatry 44:313–323
Boles SM, Miotto K (2003) Substance abuse and violence—a review of the literature. Aggress Violent Behav 8:155–174
Bond AJ (2005) Antidepressant treatments and human aggression. Eur J Pharmacol 526:218–225
Bonson KR, Johnson RG, Fiorella D, Rabin RA, Winter JC (1994) Serotonergic control of androgen-induced dominance. Pharmacol Biochem Behav 49:313–322
Bonvento G, Scatton B, Claustre Y, Rouquier L (1992) Effect of local injection of 8-OH-DPAT into the dorsal or median raphe nuclei on extracellular levels of serotonin in serotonergic projection areas in the rat brain. Neurosci Lett 137:101–104
Bouwknecht JA, Hijzen TH, van der GJ M, RA HR, Olivier B (2001) Absence of 5-HT1B receptors is associated with impaired impulse control in male 5-HT1B knockout mice. Biol Psychiatry 49:557–568
Bowery NG, Hudson AL, Price GW (1987) GABAA and GABAB receptor site distribution in the rat central nervous system. Neuroscience 20:365–383
Brahm NC, Fast GA, Brown RC (2008) Buspirone for autistic disorder in a woman with an intellectual disability. Ann Pharmacother 42:131–137
Brain PF (1979) Hormones, drugs and aggression. Montreal, Eden
Brain P, Benton D (1979) The interpretation of physiological correlates of differential housing in laboratory rats. Life Sci 24:99–115
Brown GL, Goodwin FK (1986) Cerebrospinal fluid correlates of suicide attempts and aggression. In: Mann JJ (ed) Psychobiology of Suicidal Behavior (Annals of the New York Academy of Sciences, Vol. 487). New York Academy of Sciences, New York, pp 175–220
Brunner D, Hen R (1997) Insights into the neurology of impulsive behavior from serotonin receptor knockout mice. Ann NY Acad Sci 836:81–105
Brunner HG, Nelen M, Breakefield XO, Ropers HH, Vanoost BA (1993a) Abnormal behavior associated with a point mutation in the structural gene for monoamine oxidase-A. Science 262:578–580
Brunner HG, Nelen MR, Vanzandvoort P, Abeling NGGM, Vangennip AH, Wolters EC, Kuiper MA, Ropers HH, Vanoost BA (1993b) X-Linked borderline mental-retardation with prominent behavioral disturbance—phenotype, genetic localization, and evidence for disturbed monoamine metabolism. Am J Hum Genet 52:1032–1039
Brunner D, Buhot MC, Hen R, Hofer M (1999) Anxiety, motor activation, and maternal-infant interactions in 5HT1B knockout mice. Behav Neurosci 113:587–601
Buckholtz JW, Meyer-Lindenberg A (2008) MAOA and the neurogenetic architecture of human aggression. Trends Neurosci 31:120–129
Buckley PF, Ibrahim ZY, Singer B, Orr B, Donenwirth K, Brar PS (1997) Aggression and schizophrenia: efficacy of risperidone. J Am Acad Psychiatry Law 25:173–181
Buitelaar JK, van der Gaag RJ, Cohen-Kettenis P, Melman TM (2001) A randomized controlled trial of risperidone in the treatment of aggression in hospitalized adolescents with subaverage cognitive abilities. J Clin Psychiatry 62:239–248
Burkhalter JE, Balster RL (1979) The effects of phencyclidine on isolation-induced aggression in mice. Psychol Rep 45:571–576
Burt SA, Mikolaiewski AJ (2008) Preliminary evidence that specific candidate genes are associated with adolescent-onset antisocial behavior. Aggress Behav 34:437–445
Buss AH (1961) The psychology of aggression. Wiley, New York
Buss AH, Durkee A (1957) An inventory for assessing different kinds of hostility. J Consult Psychol 21:343–349
Cadoret RJ, Langbehn D, Caspers K, Troughton EP, Yucuis R, Sandhu HK, Philibert R (2003) Associations of the serotonin transporter promoter polymorphism with aggressivity, attention deficit, and conduct disorder in an adoptee population. Compr Psychiatry 44:88–101
Cairns RB, Nakelski JS (1971) On fighting in mice: ontogenetic and experiential determinants. J Comp Physiol Psychol 74:354–364
Calabrese V, Mancuso C, Calvani M, Rizzarelli E, Butterfield DA, Stella AM (2007) Nitric oxide in the central nervous system: neuroprotection versus neurotoxicity. Nat Rev Neurosci 8:766–775
Caldwell EE, Miczek KA (2008) Long-term citalopram maintenance in mice: selective reduction of alcohol-heightened aggression. Psychopharmacology 196:407–416
Carrillo M, Ricci LA, Coppersmith GA, Melloni RH Jr (2009) The effect of increased serotonergic neurotransmission on aggression: a critical meta-analytical review of preclinical studies. Psychopharmacology 205:349–368
Cases O, Seif I, Grimsby J, Gaspar P, Chen K, Pournin S, Muller U, Aguet M, Babinet C, Shih JC, De Maeyer E (1995) Aggressive behavior and altered amounts of brain serotonin and norepinephrine in mice lacking MAOA. Science 268:1763–1766
Cases O, Vitalis T, Seif I, DeMaeyer E, Sotelo C, Gaspar P (1996) Lack of barrels in the somatosensory cortex of monoamine oxidase A-deficient mice: Role of a serotonin excess during the critical period. Neuron 16:297–307
Caspi A, McClay J, Moffitt TE, Mill J, Martin J, Craig IW, Taylor A, Poulton R (2002) Role of genotype in the cycle of violence in maltreated children. Science 297:851–854
Caspi A, Sugden K, Moffitt TE, Taylor A, Craig IW, Harrington H, McClay J, Mill J, Martin J, Braithwaite A, Poulton R (2003) Influence of life stress on depression: moderation by a polymorphism in the 5-HTT gene. Science 301:386–389
Ceglia I, Acconcia S, Fracasso C, Colovic M, Caccia S, Invernizzi RW (2004) Effects of chronic treatment with escitalopram or citalopram on extracellular 5-HT in the prefrontal cortex of rats: role of 5-HT1A receptors. Br J Pharmacol 142:469–478
Celada P, Puig MV, Casanovas JM, Guillazo G, Artigas F (2001) Control of dorsal raphe serotonergic neurons by the medial prefrontal cortex: Involvement of serotonin-1A, GABAA, and glutamate receptors. J Neurosci 21:9917–9929
Centenaro LA, Vieira K, Zimmermann N, Miczek KA, Lucion AB, de Almeida RM (2008) Social instigation and aggressive behavior in mice: role of 5-HT1A and 5-HT1B receptors in the prefrontal cortex. Psychopharmacology 201:237–248
Chalmers DT, Lovenberg TW, De Souza EB (1995) Localization of novel corticotropin-releasing factor receptor (CRF2) mRNA expression to specific subcortical nuclei in rat brain: comparison with CRF1 receptor mRNA expression. J Neurosci 15:6340–6350
Chan JP, Unger TJ, Byrnesa J, Rios M (2006) Examination of behavioral deficits triggered by targeting BDNF in fetal or postnatal brains of mice. Neuroscience 142:49–58
Chen C, Rainnie DG, Greene RW, Tonegawa S (1994) Abnormal fear response and aggressive behavior in mutant mice deficient for α-calcium-calmodulin kinase II. Science 265:291–294
Chen GL, Novak MA, Meyer JS, Kelly BJ, Vallender EJ, Miller GM (2010) The effect of rearing experience and TPH2 genotype on HPA axis function and aggression in Rhesus monkeys: a retrospective analysis. Horm Behav 57:184–191
Chen ZY, Jing D, Bath KG, Ieraci A, Khan T, Siao CJ, Herrera DG, Toth M, Yang C, McEwen BS, Hempstead BL, Lee FS (2006) Genetic variant BDNF (Val66Met) polymorphism alters anxiety-related behavior. Science 314:140–143
Cherek DR, Heistad GT (1971) Fixed-interval induced aggression. Psychon Sci 25:7–8
Cherek DR, Lane SD (1999) Laboratory and psychometric measurements of impulsivity among violent and nonviolent female parolees. Biol Psychiatry 46:273–280
Chermack ST, Giancola PR (1997) The relation between alcohol and aggression: an integrated biopsychosocial conceptualization. Clin Psychol Rev 17:621–649
Chiavegatto S, Dawson VL, Mamounas LA, Koliatsos VE, Dawson TM, Nelson RJ (2001) Brain serotonin dysfunction accounts for aggression in male mice lacking neuronal nitric oxide synthase. Proc Natl Acad Sci USA 98:1277–1281
Clotfelter ED, O’Hare EP, McNitt MM, Carpenter RE, Summers CH (2007) Serotonin decreases aggression via 5-HT1A receptors in the fighting fish Betta splendens. Pharmacol Biochem Behav 87:222–231
Coccaro EF, Kavoussi RJ (1997) Fluoxetine and impulsive aggressive behavior in personality-disordered subjects. Arch Gen Psychiatry 54:1081–1088
Coccaro EF, Kavoussi RJ, Sheline YI, Berman ME, Csernansky JG (1997) Impulsive aggression in personality disorder correlates with platelet 5- HT2A receptor binding. Neuropsychopharmacology 16:211–216
Coccaro EF, Kavoussi RJ, Hauger RL, Cooper TB, Ferris CF (1998) Cerebrospinal fluid vasopressin levels: correlates with aggression and serotonin function in personality-disordered subjects. Arch Gen Psychiatry 55:708–714
Coccaro EF, Lee R, Kavoussi RJ (2010) Aggression, suicidality, and intermittent explosive disorder: serotonergic correlates in personality disorder and healthy control subjects. Neuropsychopharmacology 35:435–444
Colmers WF, Williams JT (1988) Pertussis toxin pretreatment discriminates between pre- and postsynaptic actions of baclofen in rat dorsal raphe nucleus in vitro. Neurosci Lett 93:300–306
Cologer-Clifford A, Simon NG, Lu SF, Smoluk SA (1997) Serotonin agonist-induced decreases in intermale aggression are dependent on brain region and receptor subtype. Pharmacol Biochem Behav 58:425–430
Connor DF, Steingard RJ (1996) A clinical approach to the pharmacotherapy of aggression in children and adolescents. In Ferris CF, Grisso T (eds), Understanding Aggressive Behavior in Children. Ann NY Acad Sci 794:290-307
Crabbe JC, Phillips TJ, Feller DJ, Hen R, Wenger CD, Lessov CN, Schafer GL (1996) Elevated alcohol consumption in null mutant mice lacking 5-HT1B serotonin receptors. Nat Genet 14:98–101
Crawley JN, Schleidt WM, Contrera JF (1975) Does social environment decrease propensity to fight in male mice? Behav Biol 15:73–83
Cutler MG, Rodgers RJ, Jackson JE (1997) Behavioural effects in mice of subchronic buspirone, ondansetron, and tianeptine. I. Social interactions. Pharmacol Biochem Behav 56:287–293
Czobor P, Volavka J, Meibach RC (1995) Effect of risperidone on hostility in schizophrenia. J Clin Psychopharmacol 15:243–249
D’Adamo P, Welzl H, Papadimitriou S, Raffaele DB, Tiveron C, Tatangelo L, Pozzi L, Chapman PF, Knevett SG, Ramsay MF, Valtorta F, Leoni C, Menegon A, Wolfer DP, Lipp HP, Toniolo D (2002) Deletion of the mental retardation gene Gdi1 impairs associative memory and alters social behavior in mice. Hum Mol Genet 11:2567–2580
D’Anna KL, Stevenson SA, Gammie SC (2005) Urocortin 1 and 3 impair maternal defense behavior in mice. Behav Neurosci 119:1061–1071
DaVanzo JP, Daugherty M, Ruckart R, Kang L (1966) Pharmacological and biochemical studies in isolation-induced fighting mice. Psychopharmacologia 9:210–219
Davidson RJ, Jackson DC, Kalin NH (2000) Emotion, plasticity, context, and regulation: perspectives from affective neuroscience. Psychol Bull 126:890–909
de Almeida RMM, Lucion A (1994) Effects of intracerebroventricular administration of 5-HT receptor agonists on the maternal aggression of rats. Eur J Neurosci 264:445–448
de Almeida RMM, Lucion AB (1997) 8-OH-DPAT in the median raphe, dorsal periaqueductal gray and corticomedial amygdala nucleus decreases, but the medial septal area it can increase maternal aggressive behavior in rats. Psychopharmacology 134:392–400
de Almeida RMM, Miczek KA (2002) Aggression escalated by social instigation or by discontinuation of reinforcement (“frustration”) in mice: inhibition by anpirtoline—a 5-HT1B receptor agonist. Neuropsychopharmacology 27:171–181
de Almeida RMM, Nikulina EM, Faccidomo S, Fish EW, Miczek KA (2001) Zolmitriptan–a 5-HT1B/D agonist, alcohol, and aggression in mice. Psychopharmacology 157:131–141
de Almeida RMM, Giovenardi M, da Silva SP, de Oliveira VP, Stein DJ (2005) Maternal aggression in Wistar rats: effect of 5-HT2A/2C receptor agonist and antagonist microinjected into the dorsal periaqueductal gray matter and medial septum. Braz J Med Biol Res 38:597–602
de Almeida RM, Rosa MM, Santos DM, Saft DM, Benini Q, Miczek KA (2006) 5-HT1B receptors, ventral orbitofrontal cortex, and aggressive behavior in mice. Psychopharmacology 185:441–450
de Boer SF, Koolhaas JM (2005) 5-HT1A and 5-HT1B receptor agonists and aggression: a pharmacological challenge of the serotonin deficiency hypothesis. Eur J Pharmacol 526:125–139
de Boer SF, Lesourd M, Mocaer E, Koolhaas JM (1999) Selective antiaggressive effects of alnespirone in resident-intruder test are mediated via 5-hydroxytryptamine1A receptors: A comparative pharmacological study with 8-hydroxy-2-dipropylaminotetralin, ipsapirone, buspirone, eltoprazine, and WAY-100635. J Pharmacol Exp Ther 288:1125–1133
de Boer SF, Lesourd M, Mocaer E, Koolhaas JM (2000) Somatodendritic 5-HT1A autoreceptors mediate the anti-aggressive actions of 5-HT1A receptor agonists in rats: An ethopharmacological study with S-15535, alnespirone, and WAY-100635. Neuropsychopharmacology 23:20–33
De Deyn PP, Rabheru K, Rasmussen A, Bocksberger JP, Dautzenberg PL, Eriksson S, Lawlor BA (1999) A randomized trial of risperidone, placebo, and haloperidol for behavioral symptoms of dementia. Neurology 53:946–955
De Felipe C, Herrero JF, O’Brien JA, Palmer JA, Doyle CA, Smith AJH, Laird JMA, Belmonte C, Cervero F, Hunt SP (1998) Altered nocieption, analgesia and aggression in mice lacking the receptor for substance P. Nature 392:394–397
DeBold JF, Miczek KA (1981) Sexual dimorphism in the hormonal control of aggressive behavior of rats. Pharmacol Biochem Behav 14:89–93
Del Punta K, Leinders-Zufall T, Rodriguez I, Jukam D, Wysocki CJ, Ogawa S, Zufall F, Mombaerts P (2002) Deficient pheromone responses in mice lacking a cluster of vomeronasal receptor genes. Nature 419:70–74
Deltheil T, Guiard BP, Guilloux JP, Nicolas L, Delomenie C, Reperant C, Le Maitre E, Leroux-Nicollet I, Benmansour S, Coudore F, David DJ, Gardier AM (2008) Consequences of changes in BDNF levels on serotonin neurotransmission, 5-HT transporter expression and function: studies in adult mice hippocampus. Pharmacol Biochem Behav 90:174–183
Delville Y, Mansour KM, Ferris CF (1996) Serotonin blocks vasopressin-facilitated offensive aggression: Interactions within the ventrolateral hypothalamus of golden hamsters. Physiol Behav 59:813–816
Demas GE, Kriegsfeld LJ, Blackshaw S, Huang P, Gammie SC, Nelson RJ, Snyder SH (1999) Elimination of aggressive behavior in male mice lacking endothelial nitric oxide synthase. J Neurosci 19:1–5
Denney RM, Koch H, Craig IW (1999) Association between monoamine oxidase A activity in human male shin fibroblasts and genotype of the MAOA promoter-associated variable number tandem repeat. Hum Genet 105:542–551
DeVries AC, Young WS, Nelson RJ (1997) Reduced aggressive behaviour in mice with targeted disruption of the oxytocin gene. J Neuroendocrinol 9:363–368
Dompert WU, Glaser T, Traber J (1985) 3H-TVX Q 7821: identification of 5-HT1 binding sites as target for a novel putative anxiolytic. Naunyn Schmiedebergs Arch Pharmacol 328:467–470
Duysen EG, Stribley JA, Fry DL, Hinrichs SH, Lockridge O (2002) Rescue of the acetylcholinesterase knockout mouse by feeding a liquid diet; phenotype of the adult acetylcholinesterase deficient mouse. Brain Res Dev Brain Res 137:43–54
Egan MF, Kojima M, Callicott JH, Goldberg TE, Kolachana BS, Bertolino A, Zaitsev E, Gold B, Goldman D, Dean M, Lu B, Weinberger DR (2003) The BDNF val66met polymorphism affects activity-dependent secretion of BDNF and human memory and hippocampal function. Cell 112:257–269
Eibl-Eibesfeldt I (1950) Beiträge zur Biologie der Haus- und der Ährenmaus nebst einigen Beobachtungen an anderen Nagern. Z Tierpsychol 7:558–587
Elkabir DR, Wyatt ME, Vellucci SV, Herbert J (1990) The effects of separate or combined infusions of corticotrophin-releasing factor and vasopressin either intraventricularly or into the amygdala on aggressive and investigative behaviour in the rat. Regul Pept 28:199–214
Emeson RB, Morabito MV (2005) Food fight: the NPY-serotonin link between aggression and feeding behavior. Sci STKE 2005:e12
Faccidomo S, Bannai M, Miczek KA (2008) Escalated aggression after alcohol drinking in male mice: dorsal raphe and prefrontal cortex serotonin and 5-HT1B Receptors. Neuropsychopharmacology 33:2888–2899
Fairbanks LA, Fontenot MB, Phillips-Conroy JE, Jolly CJ, Kaplan JR, Mann JJ (1999) CSF monoamines, age and impulsivity in wild grivet monkeys (Cercopithecus aethiops aethiops). Brain Behav Evol 53:305–312
Fairbanks LA, Melega WP, Jorgensen MJ, Kaplan JR, McGuire MT (2001) Social impulsivity inversely associated with CSF 5-HIAA and fluoxetine exposure in vervet monkeys. Neuropsychopharmacology 24:370–378
Farrokhi C, Blanchard DC, Griebel G, Yang M, Gonzales C, Markham C, Blanchard RJ (2004) Effects of the CRF1 antagonist SSR125543A on aggressive behaviors in hamsters. Pharmacol Biochem Behav 77:465–469
Fava M (1997) Psychopharmacologic treatment of pathologic aggression. Psychiatr Clin North Am 20:427–451
Ferrari PF, Van Erp AMM, Tornatzky W, Miczek KA (2003) Accumbal dopamine and serotonin in anticipation of the next aggressive episode in rats. Eur J Neurosci 17:371–378
Ferris C (1992) Role of vasopressin in aggressive and dominant/subordinate behaviors. Ann NY Acad Sci 652:212–226
Ferris CF, Potegal M (1988) Vasopressin receptor blockade in the anterior hypothalamus suppresses aggression in hamsters. Physiol Behav 44:235–239
Ferris CF, Melloni RH, Koppel G, Perry KW, Fuller RW, Delville Y (1997) Vasopressin/serotonin interactions in the anterior hypothalamus control aggressive behavior in golden hamsters. J Neurosci 17:4331–4340
Ferris CF, Stolberg T, Delville Y (1999) Serotonin regulation of aggressive behavior in male golden hamsters (Mesocricetus auratus). Behav Neurosci 113:804–815
Ferris CF, Lu SF, Messenger T, Guillon CD, Heindel N, Miller M, Koppel G, Robert BF, Simon NG (2006) Orally active vasopressin V1a receptor antagonist, SRX251, selectively blocks aggressive behavior. Pharmacol Biochem Behav 83:169–174
Ferris CF, Stolberg T, Kulkarni P, Murugavel M, Blanchard R, Blanchard DC, Febo M, Brevard M, Simon NG (2008) Imaging the neural circuitry and chemical control of aggressive motivation. BMC Neurosci 9:111
Fischer HS, Zernig G, Schuligoi R, Miczek KA, Hauser KF, Gerard C, Saria A (2000) Alterations within the endogenous opioid system in mice with targeted deletion of the neutral endopeptidase (“enkephalinase”) gene. Regul Pept 96:53–58
Fish EW, Faccidomo S, Miczek KA (1999) Aggression heightened by alcohol or social instigation in mice: reduction by the 5-HT1B receptor agonist CP-94, 253. Psychopharmacology 146:391–399
Foley DL, Eaves LJ, Wormley B, Silberg JL, Maes HH, Kuhn J, Riley B (2004) Childhood adversity, monoamine oxidase A genotype, and risk for conduct disorder. Arch Gen Psychiatry 61:738–744
Forster GL, Pringle RB, Mouw NJ, Vuong SM, Watt MJ, Burke AR, Lowry CA, Summers CH, Renner KJ (2008) Corticotropin-releasing factor in the dorsal raphe nucleus increases medial prefrontal cortical serotonin via type 2 receptors and median raphe nucleus activity. Eur J Neurosci 28:299–310
Frazzetto G, Di Lorenzo G, Carola V, Proietti L, Sokolowska E, Siracusano A, Gross C, Troisi A (2007) Early trauma and increased risk for physical aggression during adulthood: the moderating role of MAOA genotype. PLoS ONE 2:e486
Fresan A, Camarena B, Apiquian R, Aguilar A, Urraca N, Nicolini H (2007) Association study of MAO-A and DRD4 genes in schizophrenic patients with aggressive behavior. Neuropsychobiology 55:171–175
Fuller RW (1996) Fluoxetine effects on serotonin function and aggressive behavior. In: Ferris CF (ed) Understanding aggressive behavior in children. The New York Academy of Sciences, New York, pp 90–97
Gallager DW, Aghajanian GK (1976) Effect of antipsychotic drugs on the firing of dorsal raphe cells. II. Reversal by picrotoxin. Eur J Pharmacol 39:357–364
Gammie SC, Nelson RJ (1999) Maternal aggression is reduced in neuronal nitric oxide synthase-deficient mice. J Neurosci 19:8027–8035
Gammie SC, Stevenson SA (2006) Intermale aggression in corticotropin-releasing factor receptor 1 deficient mice. Behav Brain Res 171:63–69
Gammie SC, Negron A, Newman SM, Rhodes JS (2004) Corticotropin-releasing factor inhibits maternal aggression in mice. Behav Neurosci 118:805–814
Gammie SC, Hasen NS, Stevenson SA, Bale TL, D'Anna KL (2005) Elevated stress sensitivity in corticotropin-releasing factor receptor 2 deficient mice decreases maternal, but not intermale aggression. Behav Brain Res 160:169–177
Gammie SC, Bethea ED, Stevenson SA (2007) Altered maternal profiles in corticotropin-releasing factor receptor 1 deficient mice. BMC Neurosci 8:17
Gervasoni D, Peyron C, Rampon C, Barbagli B, Chouvet G, Urbain N, Fort P, Luppi PH (2000) Role and origin of the GABAergic innervation of dorsal raphe serotonergic neurons. J Neurosci 20:4217–4225
Giancola PR, Levinson CA, Corman MD, Godlaski AJ, Morris DH, Phillips JP, Holt JC (2009) Men and women, alcohol and aggression. Exp Clin Psychopharmacol 17:154–164
Gimenez-Llort L, Fernandez-Teruel A, Escorihuela RM, Fredholm BB, Tobena A, Pekny M, Johansson B (2002) Mice lacking the adenosine A1 receptor are anxious and aggressive, but are normal learners with reduced muscle strength and survival rate. Eur J Neurosci 16:547–550
Godlaski AJ, Giancola PR (2009) Executive functioning, irritability, and alcohol-related aggression. Psychol Addict Behav 23:391–403
Gogos JA, Morgan M, Luine V, Santha M, Ogawa S, Pfaff D, Karayiorgou M (1998) Catechol-O-methyltransferase-deficient mice exhibit sexually dimorphic changes in catecholamine levels and behavior. Proc Natl Acad Sci USA 95:9991–9996
Goldman D, Dean M, Brown GL, Bolos AM, Tokola R, Virkkunen M, Linnoila M (1992) D2 dopamine receptor genotype and cerebrospinal fluid homovanillic acid, 5-hydroxyindoleacetic acid and 3-methoxy-4-hydroxyphenylglycol in alcoholics in Finland and the United States. Acta Psychiatr Scand 86:351–357
Goodson JL (2008) Nonapeptides and the evolutionary patterning of sociality. Prog Brain Res 170:3–15
Gowin JL, Swann AC, Moeller FG, Lane SD (2010) Zolmitriptan and human aggression: interaction with alcohol. Psychopharmacology 210:521–531
Haller J, van de Schraaf J, Kruk MR (2001) Deviant forms of aggression in glucocorticoid hyporeactive rats: a model for ‘pathological’ aggression? J Neuroendocrinol 13:102–107
Haller J, Bakos N, Rodriguiz RM, Caron MG, Wetsel WC, Liposits Z (2002) Behavioral responses to social stress in noradrenaline transporter knockout mice: effects on social behavior and depression. Brain Res Bull 58:279–284
Haller J, Mikics E, Halasz J, Toth M (2005) Mechanisms differentiating normal from abnormal aggression: glucocorticoids and serotonin. Eur J Pharmacol 526:89–100
Hallikainen T, Saito T, Lachman HM, Volavka J, Pohjalainen T, Ryynanen OP, Kauhanen J, Syvalahti E, Hietala J, Tiihonen J (1999) Association between low activity serotonin transporter promoter genotype and early onset alcoholism with habitual impulsive violent behavior. Mol Psychiatry 4:385–388
Haney M, DeBold JF, Miczek KA (1989) Maternal aggression in mice and rats towards male and female conspecifics. Aggress Behav 15:443–453
Hassanain M, Bhatt S, Siegel A (2003) Differential modulation of feline defensive rage behavior in the medial hypothalamus by 5-HT1A and 5-HT2 receptors. Brain Res 981:201–209
Haug M, Wallian L, Brain PF (1990) Effects of 8-OH-DPAT and fluoxetine on activity and attack by female mice towards lactating intruders. Gen Pharmacol 21:845–849
Heiligenberg W (1974) Processes governing behavioral states of readiness. Adv Study Behav 5:173–200
Heils A, Teufel A, Petri S, Seemann M, Bengel D, Balling U, Riederer P, Lesch KP (1995) Functional promoter and polyadenylation site mapping of the human serotonin (5-HT) transporter gene. J Neural Transm Gen Sect 102:247–254
Heils A, Teufel A, Petri S, Stober G, Riederer P, Bengel D, Lesch KP (1996) Allelic variation of human serotonin transporter gene expression. J Neurochem 66:2621–2624
Hendricks TJ, Fyodorov DV, Wegman LJ, Lelutiu NB, Pehek EA, Yamamoto B, Silver J, Weeber EJ, Sweatt JD, Deneris ES (2003) Pet-1 ETS gene plays a critical role in 5-HT neuron development and is required for normal anxiety-like and aggressive behavior. Neuron 37:233–247
Herzog H (2003) Neuropeptide Y and energy homeostasis: insights from Y receptor knockout models. Eur J Pharmacol 480:21–29
Hess WR (1954) Das Zwischenhirn. Benno Schwabe & Co., Basel
Higley JD, Suomi SJ (1986) Parental behavior in primates. In: Sluckin W (ed) Parental behavior in animals and humans. Blackwell, Oxford, pp 152–207
Higley JD, Suomi SJ, Linnoila M (1991) CSF monoamine metabolite concentrations vary according to age, rearing, and sex, and are influenced by the stressor of social separation in rhesus monkeys. Psychopharmacology 103:551–556
Higley JD, Mehlman PT, Poland RE, Taub DM, Vickers J, Suomi SJ, Linnoila M (1996) CSF testosterone and 5-HIAA correlate with different types of aggressive behaviors. Biol Psychiatry 40:1067–1082
Ho HP, Olsson M, Westberg L, Melke J, Eriksson E (2001) The serotonin reuptake inhibitor fluoxetine reduces sex steroid-related aggression in female rats: an animal model of premenstrual irritability? Neuropsychopharmacology 24:502–510
Hollander E (1999) Managing aggressive behavior in patients with obsessive-compulsive disorder and borderline personality disorder. J Clin Psychiatry 60(Suppl 15):38–44
Holmes A, Murphy DL, Crawley JN (2002) Reduced aggression in mice lacking the serotonin transporter. Psychopharmacology 161:160–167
Homberg JR, Pattij T, Janssen MC, Ronken E, De Boer SF, Schoffelmeer AN, Cuppen E (2007) Serotonin transporter deficiency in rats improves inhibitory control but not behavioural flexibility. Eur J Neurosci 26:2066–2073
Huang PL, Dawson TM, Bredt DS, Snyder SH, Fishman MC (1993) Targeted disruption of the neuronal nitric oxide synthase gene. Cell 75:1273–1286
Huang YY, Grailhe R, Arango V, Hen R, Mann JJ (1999) Relationship of psychopathology to the human serotonin1B genotype and receptor binding kinetics in postmortem brain tissue. Neuropsychopharmacology 21(2):238–246
Hurst JL (1987) Behavioral variation in wild house mice (Mus domesticus Rutty): a quantitative assessment of female social organization. Anim Behav 35:1846–1857
Innis RB, Aghajanian GK (1987) Pertussis toxin blocks 5-HT1A and GABAB receptor-mediated inhibition of serotonergic neurons. Eur J Pharmacol 143:195–204
Jarrell H, Hoffman JB, Kaplan JR, Berga S, Kinkead B, Wilson ME (2008) Polymorphisms in the serotonin reuptake transporter gene modify the consequences of social status on metabolic health in female rhesus monkeys. Physiol Behav 93:807–819
Johnson O, Becnel J, Nichols CD (2009) Serotonin 5-HT2 and 5-HT1A-like receptors differentially modulate aggressive behaviors in Drosophila melanogaster. Neuroscience 158:1292–1300
Joppa MA, Rowe RK, Meisel RL (1997) Effects of serotonin 1A or 1B receptor agonists on social aggression in male and female Syrian hamsters. Pharmacol Biochem Behav 58:349–353
Judge SJ, Ingram CD, Gartside SE (2004) GABA receptor modulation of 5-HT neuronal firing: characterization and effect of moderate in vivo variations in glucocorticoid levels. Neurochem Int 45:1057–1065
Kalen P, Pritzel M, Nieoullon A, Wiklund L (1986) Further evidence for excitatory amino acid transmission in the lateral habenular projection to the rostral raphe nuclei: lesion-induced decrease of high affinity glutamate uptake. Neurosci Lett 68:35–40
Karl T, Lin S, Schwarzer C, Sainsbury A, Couzens M, Wittmann W, Boey D, von Horsten S, Herzog H (2004) Y1 receptors regulate aggressive behavior by modulating serotonin pathways. Proc Natl Acad Sci USA 101:12742–12747
Kavoussi R, Armstead P, Coccaro E (1997) The neurobiology of impulsive aggression. Psychiatr Clin North Am 20:395–403
Keck PE Jr, Strakowski SM, McElroy SL (2000) The efficacy of atypical antipsychotics in the treatment of depressive symptoms, hostility, and suicidality in patients with schizophrenia. J Clin Psychiatry 61(Suppl 3):4–9
Khait VD, Huang YY, Zalsman G, Oquendo MA, Brent DA, Harkavy-Friedman JM, Mann JJ (2005) Association of serotonin 5-HT2A receptor binding and the T102C polymorphism in depressed and healthy Caucasian subjects. Neuropsychopharmacology 30:166–172
Kim JJ, Shih JC, Chen K, Chen L, Bao SW, Maren S, Anagnostaras SG, Fanselow MS, DeMaeyer E, Seif I, Thompson RF (1997) Selective enhancement of emotional, but not motor, learning in monoamine oxidase A-deficient mice. Proc Natl Acad Sci USA 94:5929–5933
Kim C, Jeon D, Kim YH, Lee CJ, Kim H, Shin HS (2009a) Deletion of N-type Ca2+ channel Cav2.2 results in hyperaggressive behaviors in mice. J Biol Chem 284:2738–2745
Kim YR, Jahng JW, Min SK (2009b) Association between the serotonin transporter gene (5-HTTLPR) and anger-related traits in Korean schizophrenic patients. Neuropsychobiology 59:165–171
Kim-Cohen J, Caspi A, Taylor A, Williams B, Newcombe R, Craig IW, Moffitt TE (2006) MAOA, maltreatment, and gene-environment interaction predicting children's mental health: new evidence and a meta-analysis. Mol Psychiatry 11:903–913
Kirby LG, Rice KC, Valentino RJ (2000) Effects of corticotropin-releasing factor on neuronal activity in the serotonergic dorsal raphe nucleus. Neuropsychopharmacology 22:148–162
Koleske AJ, Gifford AM, Scott ML, Nee M, Bronson RT, Miczek KA, Baltimore D (1998) Essential roles for the Abl and Arg tyrosine kinases in neurulation. Neuron 21:1259–1272
Koolhaas JM (1978) Hypothalamically induced intraspecific aggressive behaviour in the rat. Exp Brain Res 32:365–375
Koolhaas JM, Van der Brink THC, Roozendaal B, Boorsma F (1990) Medial amygdala and aggressive behavior: interaction between testosterone and vasopressin. Aggress Behav 16:223–229
Konig M, Zimmer AM, Steiner H, Holmes PV, Crawley JN, Brownstein MJ, Zimmer A (1996) Pain responses, anxiety and aggression in mice deficient in pre-proenkephalin. Nature 383:535–538
Kraemer GW, Ebert MH, Schmidt DE, McKinney WT (1989) A longitudinal study of the effect of different social rearing conditions on cerebrospinal fluid norepinephrine and biogenic amine metabolites in Rhesus monkeys. Neuropsychopharmacology 2:175–189
Kranzler HR, Hernandez-Avila CA, Gelernter J (2002) Polymorphism of the 5-HT1B receptor gene (HTR1B): strong within-locus linkage disequilibrium without association to antisocial substance dependence. Neuropsychopharmacology 26:115–122
Krsiak M (1974) Behavioral changes and aggressivity evoked by drugs in mice. Res Commun Chem Pathol Pharmacol 7:237–257
Kushi A, Sasai H, Koizumi H, Takeda N, Yokoyama M, Nakamura M (1998) Obesity and mild hyperinsulinemia found in neuropeptide Y-Y1 receptor-deficient mice. Proc Natl Acad Sci USA 95:15659–15664
Lamar M, Cutter WJ, Rubia K, Brammer M, Daly EM, Craig MC, Cleare AJ, Murphy DG (2009) 5-HT, prefrontal function and aging: fMRI of inhibition and acute tryptophan depletion. Neurobiol Aging 30:1135–1146
Lang A, Harro J, Soosaar A, Koks S, Volke V, Oreland L, Bourin M, Vasar E, Bradwejn J, Mannisto PT (1995) Role of N-methyl-D-aspartic acid and cholecystokinin receptors in apomorphine-induced aggressive behaviour in rats. Naunyn Schmiedebergs Arch Pharmacol 351:363–370
Lappalainen J, Long JC, Eggert M, Ozaki N, Robin RW, Brown GL, Naukkarinen H, Virkkunen M, Linnoila M, Goldman D (1998) Linkage of antisocial alcoholism to the serotonin 5-HT1B receptor gene in 2 populations. Arch Gen Psychiatry 55:989–994
Ledent C, Vaugeois JM, Schiffmann SN, Pedrazzini T, El Yacoubi M, Vanderhaeghen JJ, Costentin J, Heath JK, Vassart G, Parmentier M (1997) Aggressiveness, hypoalgesia and high blood pressure in mice lacking the adenosine A2a receptor. Nature 388:674–678
Lesch KP, Merschdorf U (2000) Impulsivity, aggression, and serotonin: a molecular psychobiological perspective. Behav Sci Law 18:581–604
Lesch KP, Bengel D, Heils A, Sabol SZ, Greenberg BD, Petri S, Benjamin J, Mueller CR, Hamer DH, Murphy DL (1996) Association of anxiety-related traits with a polymorphism in the serotonin transporter gene regulatory region. Science 264:1537–1551
Lesch KP, Meyer J, Glatz K, Flugge G, Hinney A, Hebebrand J, Klauck SM, Poustka A, Poustka F, Bengel D, Mossner R, Riederer P, Heils A (1997) The 5-HT transporter gene-linked polymorphic region (5-HTTLPR) in evolutionary perspective: alternative biallelic variation in Rhesus monkeys. J Neural Transm 104:1259–1266
Lerch-Haner JK, Frierson D, Crawford LK, Beck SG, Deneris ES (2008) Serotonergic transcriptional programming determines maternal behavior and offspring survival. Nat Neurosci 11:1001–1003
Levy M, Berson A, Cook T, Bollegala N, Seto E, Tursanski S, Kim J, Sockalingam S, Rajput A, Krishnadev N, Feng C, Bhalerao S (2005) Treatment of agitation following traumatic brain injury: a review of the literature. NeuroRehabilitation 20:279–306
Leyhausen P (1979) Cat behavior: predatory and social behavior of domestic and wild cats. Garland STPM, New York
Lindgren T, Kantak KM (1987) Effects of serotonin receptor agonists and antagonists on offensive aggression in mice. Aggress Behav 13:87–96
Linnoila VMI, Virkkunen M (1992) Aggression, suicidality, and serotonin. J Clin Psychiatry 53:46–51
Loconto J, Papes F, Chang E, Stowers L, Jones EP, Takada T, Kumanovics A, Fischer LK, Dulac C (2003) Functional expression of murine V2R pheromone receptors involves selective association with the M10 and M1 families of MHC class Ib molecules. Cell 112:607–618
Lonstein JS, Gammie SC (2002) Sensory, hormonal, and neural control of maternal aggression in laboratory rodents. Neurosci Biobehav Rev 26:869–888
Lowry CA, Rodda JE, Lightman SL, Ingram CD (2000) Corticotropin-releasing factor increases in vitro firing rates of serotonergic neurons in the rat dorsal raphe nucleus: evidence for activation of a topographically organized mesolimbocortical serotonergic system. J Neurosci 20:7728–7736
Lucion AB, de Almeida RMM (1996) On the dual nature of maternal aggression in rats. Aggress Behav 22:365–373
Lucki I, Wieland S (1990) 5-Hydroxytryptamine-1A receptors and behavioral responses. Neuropsychopharmacology 3:481–493
Lukkes JL, Forster GL, Renner KJ, Summers CH (2008) Corticotropin-releasing factor 1 and 2 receptors in the dorsal raphe differentially affect serotonin release in the nucleus accumbens. Eur J Pharmacol 578:185–193
Lyons WE, Mamounas LA, Ricaurte GA, Coppola V, Reid SW, Bora SH, Wihler C, Koliatsos VE, Tessarollo L (1999) Brain-derived neurotrophic factor-deficient mice develop aggressiveness and hyperphagia in conjunction with brain serotonergic abnormalities. Proc Natl Acad Sci USA 96:15239–15244
Maciewicz R, Foote WE, Bry J (1981) Excitatory projection from the interpeduncular nucleus to central superior raphe neurons. Brain Res 225:179–183
Malick JB (1979) The pharmacology of isolation-induced aggressive behavior in mice. In: Essman WB (ed) Current developments in psychopharmacology. SP Medical and Scientific Books, New York, pp 1–27
Malleret G, Hen R, Guillou JL, Segu L, Buhot MC (1999) 5-HT1B receptor knock-out mice exhibit increased exploratory activity and enhanced spatial memory performance in the Morris water maze. J Neurosci 19:6157–6168
Mandiyan VS, Coats JK, Shah NM (2005) Deficits in sexual and aggressive behaviors in Cnga2 mutant mice. Nat Neurosci 8:1660–1662
Mann JJ (1999) Role of the serotonergic system in the pathogenesis of major depression and suicidal behavior. Neuropsychopharmacology 21:99S–105S
Manuck SB, Flory JD, Ferrell RE, Mann JJ, Muldoon MF (2000) A regulatory polymorphism of the monoamine oxidase-A gene may be associated with variability in aggression, impulsivity, and central nervous system serotonergic responsivity. Psychiatry Res 95:9–23
Manuck SB, Flory JD, Muldoon MF, Ferrell RE (2002) Central nervous system serotonergic responsivity and aggressive disposition in men. Physiol Behav 77:705–709
Marino MD, Bourdelat-Parks BN, Liles LC, Weinshenker D (2005) Genetic reduction of noradrenergic function alters social memory and reduces aggression in mice. Behav Brain Res 161:197–203
Martin M, Ledent C, Parmentier M, Maldonado R, Valverde O (2002) Involvement of CB1 cannabinoid receptors in emotional behaviour. Psychopharmacology 159:379–387
Mathews TA (2004) Gene dose-dependent alterations in extraneuronal serotonin but not dopamine in mice with reduced serotonin transporter expression. J Neurosci Methods 140:169–181
Matsumoto T, Honda S, Harada N (2003) Alteration in sex-specific behaviors in male mice lacking the aromatase gene. Neuroendocrinology 77:416–424
Matsuoka Y, Furuyashiki T, Yamada K, Nagai T, Bito H, Tanaka Y, Kitaoka S, Ushikubi F, Nabeshima T, Narumiya S (2005) Prostaglandin E receptor EP1 controls impulsive behavior under stress. Proc Natl Acad Sci USA 102:16066–16071
Maxson SC, Canastar A (2007) The genetics of aggression in mice. In: Flannery D, Vazsonyi AT, Waldman I (eds) The Cambridge handbook of violent behavior and aggression. Cambridge University Press, New York, pp 91–110
McAllister KH (1990) Ethological analysis of the effects of MK-801 upon aggressive male mice: similarity to chlordiazepoxide. Pharmacol Biochem Behav 37:101–106
McBride PA, Brown RP, DeMeo M, Keilp J, Mieczkowski T, Mann JJ (1994) The relationship of platelet 5-HT2 receptor indexes to major depressive disorder, personality traits, and suicidal behavior. Biol Psychiatry 35:295–308
McKenzie-Quirk SD, Girasa KA, Allan AM, Miczek KA (2005) 5-HT3 receptors, alcohol and aggressive behavior in mice. Behav Pharmacol 16:163–170
McKinley JC, Hathaway SR, Meehl PE (1948) The Minnesota multiphasic personality inventory: the K-scale. J Consult Psychol 12:20–31
McMillen BA, DaVanzo EA, Scott SM, Song AH (1988) N-alkyl-substituted aryl-piperazine drugs: relationship between affinity for serotonin receptors and inhibition of aggression. Drug Dev Res 12:53–62
Mehlman PT, Higley JD, Faucher I, Lilly AA, Taub DM, Vickers J, Suomi SJ, Linnoila M (1994) Low CSF 5-HIAA concentrations and severe aggression and impaired impulse control in nonhuman primates. Am J Psychiatry 151:1485–1491
Meloni EG, Reedy CL, Cohen BM, Carlezon WA Jr (2008) Activation of raphe efferents to the medial prefrontal cortex by corticotropin-releasing factor: correlation with anxiety-like behavior. Biol Psychiatry 63:832–839
Mendoza DL, Bravo HA, Swanson HH (1999) Antiaggresive and anxiolytic effects of gepirone in mice, and their attenuation by WAY 100635. Pharmacol Biochem Behav 62:499–509
Meyer-Lindenberg A, Buckholtz JW, Kolachana B, Hariri AR, Pezawas L, Blasi G, Wabnitz A, Honea R, Verchinski B, Callicott JH, Egan M, Mattay V, Weinberger DR (2006) Neural mechanisms of genetic risk for impulsivity and violence in humans. Proc Natl Acad Sci USA 103:6269–6274
Miczek KA (1987) The psychopharmacology of aggression. In: Iversen LL, Iversen SD, Snyder SH (eds) Handbook of Psychopharmacology: New directions in behavioral pharmacology, vol 19. Plenum, New York, pp 183–328
Miczek KA, Haney M (1994) Psychomotor stimulant effects of d-amphetamine, MDMA and PCP: aggressive and schedule-controlled behavior in mice. Psychopharmacology 115:358–365
Miczek KA, O’Donnell JM (1978) Intruder-evoked aggression in isolated and nonisolated mice: effects of psychomotor stimulants and l-dopa. Psychopharmacology 57:47–55
Miczek KA, de Almeida RMM (2001) Oral drug self-administration in the home cage of mice: alcohol- heightened aggression and inhibition by the 5-HT1B agonist anpirtoline. Psychopharmacology 157:421–429
Miczek KA, Weerts EM, Tornatzky W, DeBold JF, Vatne TM (1992) Alcohol and “bursts” of aggressive behavior: ethological analysis of individual differences in rats. Psychopharmacology 107:551–563
Miczek KA, Barros HM, Sakoda L, Weerts EM (1998a) Alcohol and heightened aggression in individual mice. Alcohol Clin Exp Res 22:1698–1705
Miczek KA, Hussain S, Faccidomo S (1998b) Alcohol-heightened aggression in mice: attenuation by 5-HT1A receptor agonists. Psychopharmacology 139:160–168
Miczek KA, Maxson SC, Fish EW, Faccidomo S (2001) Aggressive behavioral phenotypes in mice. Behav Brain Res 125:167–181
Miczek KA, Fish EW, DeBold JF, de Almeida RMM (2002) Social and neural determinants of aggressive behavior: pharmacotherapeutic targets at serotonin, dopamine and γ-aminobutyric acid systems. Psychopharmacology 163:434–458
Miczek KA, Fish EW, De Bold JF (2003) Neurosteroids, GABAA receptors, and escalated aggressive behavior. Horm Behav 44:242–257
Miczek KA, Faccidomo S, de Almeida RMM, Bannai M, Fish EW, DeBold JF (2004) Escalated aggressive behavior: new pharmacotherapeutic approaches and opportunities. Ann NY Acad Sci 1036:336–355
Miczek KA, de Almeida RMM, Kravitz EA, Rissman EF, de Boer SF, Raine A (2007a) Neurobiology of escalated aggression and violence. J Neurosci 27:11803–11806
Miczek KA, Faccidomo SP, Fish EW, DeBold JF (2007b) Neurochemistry and molecular neurobiology of aggressive behavior. In: Blaustein J (ed) Behavioral neurochemistry, neuroendocrinology and molecular neurobiology. Springer, New York, pp 285–336
Mitchell PJ (2005) Antidepressant treatment and rodent aggressive behaviour. Eur J Pharmacol 526:147–162
Mitchell PJ, Redfern PH (1992) Acute and chronic antidepressant drug treatments induce opposite effects in the social behavior of rats. J Psychopharmacol 6:241–257
Mitchell PJ, Redfern PH (1997) Potentiation of the time-dependent, antidepressant-induced changes in the agonistic behaviour of resident rats by the 5-HT1A receptor antagonist, WAY-100635. Behav Pharmacol 8:585–606
Mitchell PJ, Fletcher A, Redfern PH (1991) Is antidepressant efficacy revealed by drug-induced changes in rat behaviour exhibited during social interaction? Neurosci Biobehav Rev 15:539–544
Miyakawa T, Yagi T, Takao K, Niki H (2001) Differential effect of Fyn tyrosine kinase deletion on offensive and defensive aggression. Behav Brain Res 122:51–56
Morgan C, Thomas RE, Ma W, Novotny MV, Cone RD (2004) Melanocortin-5 receptor deficiency reduces a pheromonal signal for aggression in male mice. Chem Senses 29:111–115
Mos J, Olivier B, Poth M, Van Oorschot R, Van Aken H (1993) The effects of dorsal raphe administration of eltoprazine, TFMPP and 8-OH- DPAT on resident intruder aggression in the rat. Eur J Pharmacol 238:411–415
Muehlenkamp F, Lucion A, Vogel WH (1995) Effects of selective serotenergic agonists on aggressive behavior in rats. Pharmacol Biochem Behav 50:671–674
Murphy DL, Lesch KP (2008) Targeting the murine serotonin transporter: insights into human neurobiology. Nat Rev Neurosci 9:85–96
Musty RE, Consroe PF (1982) Phencyclidine produces aggressive behavior in rapid eye movement sleep- deprived rats. Life Sci 30:1733–1738
Nagtegaal MH, Rassin E (2004) The usefulness of the thought suppression paradigm in explaining impulsivity and aggression. Pers Individ Differ 37:1233–1244
Nanopoulos D, Belin MF, Maitre M, Vincendon G, Pujol JF (1982) Immunocytochemical evidence for the existence of GABAergic neurons in the nucleus raphe dorsalis. Possible existence of neurons containing serotonin and GABA. Brain Res 232:375–389
Natarajan D, Caramaschi D (2010) Animal violence demystified. Front Behav Neurosci 4:9
Nelson RJ, Chiavegatto S (2001) Molecular basis of aggression. Trends Neurosci 24:713–719
Nelson RJ, Demas GE, Huang PL, Fishman MC, Dawson VL, Dawson TM, Snyder SH (1995) Behavioural abnormalities in male mice lacking neuronal nitric oxide synthase. Nature 378:383–386
Neumann ID, Veenema AH, Beiderbeck DI (2010) Aggression and anxiety: social context and neurobiological links. Front Behav Neurosci 4:12
Neves-Pereira M, Mundo E, Muglia P, King N, Macciardi F, Kennedy JL (2002) The brain-derived neurotrophic factor gene confers susceptibility to bipolar disorder: Evidence from a family-based association study. Am J Hum Genet 71:651–655
New AS, Buchsbaum MS, Hazlett EA, Goodman M, Koenigsberg HW, Lo J, Iskander L, Newmark R, Brand J, Flynn K, Siever LJ (2004) Fluoxetine increases relative metabolic rate in prefrontal cortex in impulsive aggression. Psychopharmacology 176:451–458
Newman TK, Syagailo YV, Barr CS, Wendland JR, Champoux M, Graessle M, Suomi SJ, Higley JD, Lesch KP (2005) Monoamine oxidase A gene promoter variation and rearing experience influences aggressive behavior in rhesus monkeys. Biol Psychiatry 57:167–172
Nicot A, Otto T, Brabet P, Dicicco-Bloom EM (2004) Altered social behavior in pituitary adenylate cyclase-activating polypeptide type I receptor-deficient mice. J Neurosci 24:8786–8795
Nikulina EM, Avgustinovich DF, Popova NK (1992) Role of 5HT1A receptors in a variety of kinds of aggressive behavior in wild rats and counterparts selected for low defensiveness towards Man. Aggress Behav 18:357–364
Nogueira RL, Graeff FG (1995) Role of 5HT receptor subtypes in the modulation of dorsal periaqueductal gray generated aversion. Pharmacol Biochem Behav 52:1–6
Noirot E, Goyens J, Buhot MC (1975) Aggressive behavior of pregnant mice towards males. Horm Behav 6:9–17
Nomura M, Kusumi I, Kaneko M, Masui T, Daiguji M, Ueno T, Koyama T, Nomura Y (2006) Involvement of a polymorphism in the 5-HT2A receptor gene in impulsive behavior. Psychopharmacology 187:30–35
Oades RD, Lasky-Su J, Christiansen H, Faraone SV, Sonuga-Barke EJS, Banaschewski T, Chen W, Anney RJL, Buitelaar JK, Ebstein RP, Franke B, Gill M, Miranda A, Roeyers H, Rothenberger A, Sergeant JA, Steinhausen HC, Taylor EA, Thompson M, Asherson P (2008) The influence of serotonin- and other genes on impulsive behavioral aggression and cognitive impulsivity in children with attention-deficit/hyperactivity disorder (ADHD): Findings from a family-based association test (FBAT) analysis. Behav Brain Funct 4:48
Ogawa S, Eng V, Taylor J, Lubahn DB, Korach KS, Pfaff DW (1998a) Roles of estrogen receptor-β gene expression in reproduction-related behaviors in female mice. Endocrinology 139:5070–5081
Ogawa S, Washburn TF, Taylor J, Lubahn DB, Korach KS, Pfaff DW (1998b) Modifications of testosterone-dependent behaviors by estrogen receptor-β gene disruption in male mice. Endocrinology 139:5058–5069
Ogawa S, Chan J, Chester AE, Gustafsson J-A, Korach KS, Pfaff DW (1999) Survival of reproductive behaviors in estrogen receptor β gene-deficient (βERKO) male and female mice. Proc Natl Acad Sci USA 96:12887–12892
Olivier B (2004) Serotonin and aggression. Ann NY Acad Sci 1036:382–392
Olivier B, Mos J, Van der Heyden J, Hartog J (1989) Serotonergic modulation of social interactions in isolated male mice. Psychopharmacology 97:154–156
Olivier B, Mos J, Rasmussen D (1990) Behavioural pharmacology of the serenic, eltoprazine. Rev Drug Metab Drug Interact 8:31–83
Olivier B, Mos J, Tulp MTM, van der Poel AM (1992) Animal models of anxiety and aggression in the study of serotonergic agents. In: Langer SZ (ed) Serotonin receptor subtypes: Pharmacological significance and clinical implications. Karger, Basel, pp 67–79
Olivier B, Mos J, Van Oorschot R, Hen R (1995) Serotonin receptors and animal models of aggressive behavior. Pharmacopsychiatry 28:80–90
Oliveira-dos-Santos AJ, Matsumoto G, Snow BE, Bai D, Houston FP, Whishaw IQ, Mariathasan S, Sasaki T, Wakeham A, Ohashi PS, Roder JC, Barnes CA, Siderovski DP, Penninger JM (2000) Regulation of T cell activation, anxiety, and male aggression by RGS2. Proc Natl Acad Sci USA 97:12272–12277
Oquendo MA, Russo SA, Underwood MD, Kassir SA, Ellis SP, Mann JJ, Arango V (2006) Higher postmortem prefrontal 5-HT2A receptor binding correlates with lifetime aggression in suicide. Biol Psychiatry 59:235–243
Pabis DJ, Stanislav SW (1996) Pharmacotherapy of aggressive behavior. Ann Pharmacother 30:278–287
Palanza P, Della Seta D, Ferrari PF, Parmigiani S (2005) Female competition in wild house mice depends upon timing of female/male settlement and kinship between females. Anim Behav 69:1259–1271
Pallotta M, Segieth J, Whitton PS (1998) N-Methyl-d-aspartate receptors regulate 5-HT release in the raphe nuclei and frontal cortex of freely moving rats: differential role of 5-HT1A autoreceptors. Brain Res 783:173–178
Parmigiani S, Ferrari PF, Palanza P (1998) An evolutionary approach to behavioral pharmacology: using drugs to understand proximate and ultimate mechanisms of different forms of aggression in mice. Neurosci Biobehav Rev 23:143–153
Passamonti L, Cerasa A, Gioia MC, Magariello A, Muglia M, Quattrone A, Fera F (2008) Genetically dependent modulation of serotonergic inactivation in the human prefrontal cortex. Neuroimage 40:1264–1273
Peeke HVS, Figler MH (1981) Modulation of aggressive behavior in fish by alcohol and congeners. Pharmacol Biochem Behav 14(Suppl 1):79–84
Pellis SM, Pellis VC (1988) Play-fighting in the Syrian golden hamster Mesocricetus auratus Waterhouse, and its relationship to serious fighting during postweaning development. Dev Psychobiol 21:323–337
Pineyro G, Blier P, Dennis T, de Montigny C (1994) Desensitization of the neuronal 5-HT carrier following its long-term blockade. J Neurosci 14:3036–3047
Pinna G, Dong E, Matsumoto K, Costa E, Guidotti A (2003) In socially isolated mice, the reversal of brain allopregnanolone down-regulation mediates the anti-aggressive action of fluoxetine. Proc Natl Acad Sci USA 100:2035–2040
Pinna G, Costa E, Guidotti A (2006) Fluoxetine and norfluoxetine stereospecifically and selectively increase brain neurosteroid content at doses that are inactive on 5-HT reuptake. Psychopharmacology 186:362–372
Popova NK, Avgustinovich DF, Kolpakov VG, Plyusnina IZ (1998) Specific [3H]8-OH-DPAT binding in brain regions of rats genetically predisposed to various defense behavior strategies. Pharmacol Biochem Behav 59:793–797
Potegal M (1991) Attack priming and satiation in female golden hamsters: tests of some alternatives to the aggression arousal interpretation. Aggress Behav 17:327–335
Potegal M, Tenbrink L (1984) Behavior of attack-primed and attack-satiated female golden hamsters (Mesocricetus auratus). J Comp Psychol 98:66–75
Potter E, Sutton S, Donaldson C, Chen R, Perrin M, Lewis K, Sawchenko PE, Vale W (1994) Distribution of corticotropin-releasing factor receptor mRNA expression in the rat brain and pituitary. Proc Natl Acad Sci USA 91:8777–8781
Price ML, Lucki I (2001) Regulation of serotonin release in the lateral septum and striatum by corticotropin-releasing factor. J Neurosci 21:2833–2841
Price ML, Curtis AL, Kirby LJ, Valentino RJ, Lucki I (1998) Effects of corticotropin-releasing factor on brain serotonergic activity. Neuropsychopharmacology 18:492–502
Quadros IM, Miguel TM, DeBold JF, Miczek KA (2009a) Opposing action of CRF1 vs. CRF2 receptors in the dorsal raphé: modulation of alcohol-heightened aggression. Program No.445.5/T8. 2009 Neuroscience Meeting Planner. Chicago, IL: Society for Neuroscience. Online
Quadros IM, Takahashi A, Miczek KA (2009b) Serotonin and aggression. In: Müller CP, Jacobs BL (eds) Handbook of the Behavioral Neurobiology of Serotonin. Academic Press, London, pp 687–714
Raine A (2002) Biosocial studies of antisocial and violent behavior in children and adults: a review. J Abnorm Child Psychol 30:311–326
Ratey JJ, O’Driscoll GA (1989) Buspirone as a habilitative drug for patients with a dual diagnosis. Fam Pract Recertif 11:38–45
Ratey JJ, Sovner R, Mikkelsen E, Chmielinski HE (1989) Buspirone therapy for maladaptive behavior and anxiety in developmentally disabled persons. J Clin Psychiatry 50:382–384
Raj YP (2004) Psychopharmacology of borderline personality disorder. Curr Psychiatry Rep 6:225–231
Ramboz S, Saudou F, Amara DA, Belzung C, Segu L, Misslin R, Buhot MC, Hen R (1995) 5-HT1B receptor knock out—Behavioral consequences. Behav Brain Res 73:305–312
Rasia-Filho AA, Giovenardi M, de Almeida RM (2008) Drugs and aggression. Recent Pat CNS Drug Discov 3:40–49
Raskin K, de Gendt K, Duittoz A, Liere P, Verhoeven G, Tronche F, Mhaouty-Kodja S (2009) Conditional inactivation of androgen receptor gene in the nervous system: effects on male behavioral and neuroendocrine responses. J Neurosci 29:4461–4470
Ratey J, Sovner R, Parks A, Rogentine K (1991) Buspirone treatment of aggression and anxiety in mentally retarded patients: a multiple-baseline, placebo lead-in study. J Clin Psychiatry 52:159–162
Reist C, Nakamura K, Sagart E, Sokolski KN, Fujimoto KA (2003) Impulsive aggressive behavior: open-label treatment with citalopram. J Clin Psychiatry 64:81–85
Rewerski W, Kostowski W, Piechocki T, Rylski M (1971) The effects of some hallucinogens on aggressiveness of mice and rats. I. Pharmacology 5:314–320
Ricci LA, Grimes JM, Melloni RH Jr (2004) Serotonin type 3 receptors modulate the aggression-stimulating effects of adolescent cocaine exposure in Syrian hamsters (Mesocricetus auratus). Behav Neurosci 118:1097–1110
Rios M, Lambe EK, Liu RJ, Teillon S, Liu JH, Akbarian S, Roffler-Tarlov S, Jaenisch R, Aghajanian GK (2006) Severe deficits in 5-HT2A-mediated neurotransmission in BDNF conditional mutant mice. J Neurobiol 66:408–420
Rocha BA, Scearce-Levie K, Lucas JJ, Hiroi N, Castanon N, Crabbe JC, Nestler EJ, Hen R (1998) Increased vulnerability to cocaine in mice lacking the serotonin-1B receptor. Nature 393:175–178
Rodriguez-Arias M, Minarro J, Aguilar MA, Pinazo J, Simon VM (1998) Effects of risperidone and SCH 23390 on isolation-induced aggression in male mice. Eur Neuropsychopharmacol 8:95–103
Rodriguiz RM, Chu R, Caron MG, Wetsel WC (2004) Aberrant responses in social interaction of dopamine transporter knockout mice. Behav Brain Res 148:185–198
Rudissaar R, Pruus K, Skrebuhhova T, Allikmets L, Matto V (1999) Modulatory role of 5- HT3 receptors in mediation of apomorphine-induced aggressive behaviour in male rats. Behav Brain Res 106:91–96
Rydén E, Thase ME, Straht D, Aberg-Wistedt A, Bejerot S, Landen M (2009) A history of childhood attention-deficit hyperactivity disorder (ADHD) impacts clinical outcome in adult bipolar patients regardless of current ADHD. Acta Psychiatr Scand 120:239–246
Sabol SZ, Hu S, Hamer D (1998) A functional polymorphism in the monoamine oxidase A gene promoter. Hum Genet 103:273–279
Sakaue M, Ago Y, Sowa C, Sakamoto Y, Nishihara B, Koyama Y, Baba A, Matsuda T (2002) Modulation by 5-HT2A receptors of aggressive behavior in isolated mice. Jpn J Pharmacol 89:89–92
Sallinen J, Haapalinna A, Viitamaa T, Kobilka BK, Scheinin M (1998) Adrenergic α2c-receptors modulate the acoustic startle reflex, prepulse inhibition, and aggression in mice. J Neurosci 18:3035–3042
Sanchez C, Hyttel J (1994) Isolation-induced aggression in mice: effects of 5- hydroxytryptamine uptake inhibitors and involvement of postsynaptic 5-HT1A receptors. Eur J Pharmacol 264:241–247
Sanchez C, Meier E (1997) Behavioral profiles of SSRIs in animal models of depression, anxiety and aggression. Psychopharmacology 129:197–205
Sanchez C, Arnt J, Hyttel J, Moltzen EK (1993) The role of serotonergic mechanisms in inhibition of isolation-induced aggression in male mice. Psychopharmacology 110:53–59
Sano Y, Ornthanalai VG, Yamada K, Homma C, Suzuki H, Suzuki T, Murphy NP, Itohara S (2009) X11-like protein deficiency is associated with impaired conflict resolution in mice. J Neurosci 29:5884–5896
Saudou F, Amara DA, Dierich A, Lemeur M, Ramboz S, Segu L, Buhot MC, Hen R (1994) Enhanced aggressive behavior in mice lacking 5-HT1B receptor. Science 265:1875–1878
Scott AL, Bortolato M, Chen K, Shih JC (2008) Novel monoamine oxidase A knock out mice with human-like spontaneous mutation. NeuroReport 19:739–743
Sgoifo A, Stilli D, Musso E, Mainardi D, Parmigiani S (1992) Offensive and defensive bite-target topographies in attacks by lactating rats. Aggress Behav 17:47–52
Shaikh MB, De Lanerolle NC, Siegel A (1997) Serotonin 5-HT1A and 5-HT2/1C receptors in the midbrain periaqueductal gray differentially modulate defensive rage behavior elicited from the medial hypothalamus of the cat. Brain Res 765:198–207
Shih JC, Ridd MJ, Chen K, Meehan WP, Kung MP, Seif I, De Maeyer E (1999) Ketanserin and tetrabenazine aggression in mice lacking monoamine oxidase A. Brain Res 835:104–112
Siegel A, Roeling TAP, Gregg TR, Kruk MR (1999) Neuropharmacology of brain-stimulation-evoked aggression. Neurosci Biobehav Rev 23:359–389
Sijbesma H, Schipper J, De Kloet ER, Mos J, Van Aken H, Olivier B (1991) Postsynaptic 5-HT1 receptors and offensive aggression in rats: a combined behavioural and autoradiographic study with eltoprazine. Pharmacol Biochem Behav 38:447–458
Silva AJ, Paylor R, Wehner JM, Tonegawa S (1992) Impaired spatial learning in α-calcium-calmodulin kinase II mutant mice. Science 257:206–211
Sinha R, Cloninger CR, Parsian A (2003) Linkage disequilibrium and haplotype analysis between serotonin receptor 1B gene variations and subtypes of alcoholism. Am J Med Genet B Neuropsychiatr Genet 121B:83–88
Sjoberg RL, Nilsson KW, Wargelius HL, Leppert J, Lindstrom L, Oreland L (2007) Adolescent girls and criminal activity: Role of MAOA-LPR genotype and psychosicial factors. Am J Med Genet B Neuropsychiatr Genet 144B:159–164
Smuts BB (1986) Sexual competition and mate choice. In: Smuts BB, Cheney DL, Seyfarth RM, Wrangham RW, Struhsaker TT (eds) Primate societies. University of Chicago Press, Chicago, pp 385–399
Sofia RD (1969) Structural relationship and potency of agents which selectively block mouse killing (muricide) behavior in rats. Life Sci 8:1201–1210
Sperry TS, Thompson CK, Wingfield JC (2003) Effects of acute treatment with 8-OH-DPAT and fluoxetine on aggressive behaviour in male song sparrows (Melospiza melodia morphna). J Neuroendocrinol 15:150–160
Spielberg CD, Sharma S, Singh M (1973) Development of Hindi edition of state-trait anxiety inventory. Indian J Psychol 48:11–20
Spigset O (1999) Adverse reactions of selective serotonin reuptake inhibitors—reports from a spontaneous reporting system. Drug Saf 20:277–287
Sprouse JS, Aghajanian GK (1987) Electrophysiological responses of serotoninergic dorsal raphe neurons to 5-HT1A and 5-HT1B agonists. Synapse 1:3–9
Steiniger F (1950) Beitrag zur Soziologie und sonstigen Biologie der Wanderratte. Z Tierpsychol 7:356–379
Stoff DM, Vitiello B (1996) Role of serotonin in aggression of children and adolesecents: biochemical and phamacological studies. In: Stoff DM (ed) Aggression and violence: Genetic, neurobiological and biosocial perspectives. Lawrence Erlbaum Associates, Mahwah, pp 101–123
Stork O, Welzl H, Cremer H, Schachner M (1997) Increased intermale aggression and neuroendocrine response in mice deficient for the neural cell adhesion molecule (NCAM). Eur J Neurosci 9:1117–1125
Stork O, Ji FY, Kaneko K, Stork S, Yoshinobu Y, Moriya T, Shibata S, Obata K (2000) Postnatal development of a GABA deficit and disturbance of neural functions in mice lacking GAD65. Brain Res 865:45–58
Stowers L, Holy TE, Meister M, Dulac C, Koentges G (2002) Loss of sex discrimination and male-male aggression in mice deficient for TRP2. Science 295:1493–1500
Sun HF, Chang YT, Fann CS, Chang CJ, Chen YH, Hsu YP, Yu WY, Cheng AT (2002) Association study of novel human serotonin 5-HT1B polymorphisms with alcohol dependence in Taiwanese Han. Biol Psychiatry 51:896–901
Swanson LW, Sawchenko PE, Rivier J, Vale WW (1983) Organization of ovine corticotropin-releasing factor immunoreactive cells and fibers in the rat brain: an immunohistochemical study. Neuroendocrinology 36:165–186
Swanson JW, Swartz MS, Van Dorn RA, Volavka J, Monahan J, Stroup TS, Mcevoy JP, Wagner HR, Elbogen EB, Lieberman JA (2008) Comparison of antipsychotic medication effects on reducing violence in people with schizophrenia. Br J Psychiatry 193:37–43
Takahashi A, Kwa C, DeBold JF, Miczek KA (2010a) GABAA receptors in the dorsal raphé nucleus of mice: escalation of aggression after alcohol consumption. Psychopharmacology 211:467–477
Takahashi A, Shimamoto A, Boyson CO, DeBold JF, Miczek KA (2010b) GABAB receptor modulation of serotonin neurons in the dorsal raphé nucleus and escalation of aggression in mice. J Neurosci (in press)
Takayanagi Y, Yoshida M, Bielsky IF, Ross HE, Kawamata M, Onaka T, Yanagisawa T, Kimura T, Matzuk MM, Young LJ, Nishimori K (2005) Pervasive social deficits, but normal parturition, in oxytocin receptor-deficient mice. Proc Natl Acad Sci USA 102:16096–16101
Tao R, Auerbach SB (2000) Regulation of serotonin release by GABA and excitatory amino acids. J Psychopharmacol 14:100–113
Tao R, Ma Z, Auerbach SB (1996) Differential regulation of 5-hydroxytryptamine release by GABAA and GABAB receptors in midbrain raphe nuclei and forebrain of rats. Br J Pharmacol 119:1375–1384
Taylor SP (1967) Aggressive behavior and physiological arousal as a function of provocation and the tendency to inhibit aggression. J Pers 35:297–310
Tazi A, Dantzer R, Le Moal M, Rivier J, Vale W, Koob GF (1987) Corticotropin-releasing factor antagonist blocks stress-induced fighting in rats. Regul Pept 18:37–42
Ten Eyck GR (2008) Serotonin modulates vocalizations and territorial behavior in an amphibian. Behav Brain Res 193:144–147
Tompkins EC, Clemento AJ, Taylor DP, Perhach JL Jr (1980) Inhibition of aggressive behavior in Rhesus monkeys by buspirone. Res Commun Psychol Psych Behav 5:337–352
Troisi A, Vicario E, Nuccetelli F, Ciani N, Pasini A (1995) Effects of fluoxetine on aggressive behavior of adult inpatients with mental retardation and epilepsy. Pharmacopsychiatry 28:1–4
Tsai SJ, Liao DL, Yu YW, Chen TJ, Wu HC, Lin CH, Cheng CY, Hong CJ (2005) A study of the association of (Val66Met) polymorphism in the brain-derived neurotrophic factor gene with alcohol dependence and extreme violence in Chinese males. Neurosci Lett 381:340–343
Tyler CB, Miczek KA (1982) Effects of phencyclidine on aggressive behavior in mice. Pharmacol Biochem Behav 17:503–510
Tyrer P, Oliver-Africano PC, Ahmed Z, Bouras N, Cooray S, Deb S, Murphy D, Hare M, Meade M, Reece B, Kramo K, Bhaumik S, Harley D, Regan A, Thomas D, Rao B, North B, Eliahoo J, Karatela S, Soni A, Crawford M (2008) Risperidone, haloperidol, and placebo in the treatment of aggressive challenging behaviour in patients with intellectual disability: a randomised controlled trial. Lancet 371:57–63
Valentino RJ, Commons KG (2005) Peptides that fine-tune the serotonin system. Neuropeptides 39:1–8
Valzelli L (1977) About a “specific” neurochemistry of aggressive behavior. In: Delgado JMR (ed) Behavioral neurochemistry. Spectrum Publications, Inc., New York, pp 113–132
Valzelli L, Bernasconi S (1979) Aggressiveness by isolation and brain serotonin turnover changes in different strains of mice. Neuropsychobiology 5:129–135
Valzelli L, Giacalone E, Garattini S (1967) Pharmacological control of aggressive behavior in mice. Eur J Pharmacol 2:144–146
Van den Berg L, Vos-Loohuis M, Schilder MBH, van Oost BA, Hazewinkel HAW, Wade CM, Karlsson EK, Lindblad-Toh K, Liinamo AE, Leegwater PAJ (2008) Evaluation of the serotonergic genes htr1A, htr1B, htr2A, and slc6A4 in aggressive behavior of golden retriever dogs. Behav Genet 38:55–66
Van Der Vegt BJ, Lieuwes N, van de Wall EH, Kato K, Moya-Albiol L, Martinez-Sanchis S, de Boer SF, Koolhaas JM (2003) Activation of serotonergic neurotransmission during the performance of aggressive behavior in rats. Behav Neurosci 117:667–674
Van Erp AMM, Miczek KA (2000) Aggressive behavior, increased accumbal dopamine, and decreased cortical serotonin in rats. J Neurosci 20:9320–9325
van Oortmerssen GA, Bakker TCM (1981) Artificial selection for short and long attack latencies in wild Mus musculus domesticus. Behav Genet 11:115–126
Vandenbergh JG (1967) The development of social structure in free-ranging Rhesus monkeys. Behaviour 29:179–194
Vandermaelen CP, Matheson GK, Wilderman RC, Patterson LA (1986) Inhibition of serotonergic dorsal raphe neurons by systemic and iontophoretic administration of buspirone, a non-benzodiazepine anxiolytic drug. Eur J Pharmacol 129:123–130
Veiga CP, Miczek KA, Lucion AB, de Almeida RMM (2007) Effect of 5-HT1B receptor agonists injected into the prefrontal cortex on maternal aggression in rats. Braz J Med Biol Res 40:825–830
Veiga CP, Miczek KA, Lucion AB, de Almeida RMM (2010) Social Instigation and maternal aggression in rats: role of 5-HT1A and 5-HT1B receptors in the dorsal raphé nucleus and prefrontal cortex. Psychopharmacology (submitted)
Vekovischeva OY, Aitta-aho T, Echenko O, Kankaanpaa A, Seppala T, Honkanen A, Sprengel R, Korpi ER (2004) Reduced aggression in AMPA-type glutamate receptor GluR-A subunit-deficient mice. Genes Brain Behav 3:253–265
Vitiello B, Stoff DM (1997) Subtypes of aggression and their relevance to child psychiatry. J Am Acad Child Adolesc Psychiatry 36:307–315
Volavka J, Czobor P, Citrome L, McQuade RD, Carson WH, Kostic D, Hardy S, Marcus R (2005) Efficacy of aripiprazole against hostility in schizophrenia and schizoaffective disorder: data from 5 double-blind studies. J Clin Psychiatry 66:1362–1366
Walsh MT, Dinan TG (2001) Selective serotonin reuptake inhibitors and violence: a review of the available evidence. Acta Psychiatr Scand 104:84–91
Wang QP, Ochiai H, Nakai Y (1992) GABAergic innervation of serotonergic neurons in the dorsal raphe nucleus of the rat studied by electron microscopy double immunostaining. Brain Res Bull 29:943–948
Weder N, Yang BZ, Douglas-Palumberi H, Massey J, Krystal JH, Gelernter J, Kaufman J (2009) MAOA genotype, maltreatment, and aggressive behavior: the changing impact of genotype at varying levels of trauma. Biol Psychiatry 65:417–424
Welch BL, Welch AS (1968) Rapid modification of isolation-induced aggressive behavior and elevation of brain catecholamines and serotonin by the quick-acting monoamine- oxidase inhibitor pargyline. Commun Behav Biol 1:347–351
Wersinger SR, Ginns EI, O’Carroll AM, Lolait SJ, Young WS III (2002) Vasopressin V1b receptor knockout reduces aggressive behavior in male mice. Mol Psychiatry 7:975–984
Whale R, Quested DJ, Laver D, Harrison PJ, Cowen PJ (2000) Serotonin transporter (5-HTT) promoter genotype may influence the prolactin response to clomipramine. Psychopharmacology 150:120–122
White SM, Kucharik RF, Moyer JA (1991) Effects of serotonergic agents on isolation-induced aggression. Pharmacol Biochem Behav 39:729–736
Widom CS, Brzustowicz LM (2006) MAOA and the “cycle of violence”: childhood abuse and neglect, MAOA genotype, and risk for violent and antisocial behavior. Biol Psychiatry 60:684–689
Wilmot CA, Vander Wende C, Spoerlein MT (1987) The effects of phencyclidine on fighting in differentially housed mice. Pharmacol Biochem Behav 28:341–346
Winslow JT, Hastings N, Carter CS, Harbaugh CR, Insel TR (1993) A role for central vasopressin in pair bonding in monogamous prairie voles. Nature 365:545–548
Winslow JT, Hearn EF, Ferguson J, Young LJ, Matzuk MM, Insel TR (2000) Infant vocalization, adult aggression, and fear behavior of an oxytocin null mutant mouse. Horm Behav 37:145–155
Witte AV, Floel A, Stein P, Savli M, Mien LK, Wadsak W, Spindelegger C, Moser U, Fink M, Hahn A, Mitterhauser M, Kletter K, Kasper S, Lanzenberger R (2009) Aggression is related to frontal serotonin-1A receptor distribution as revealed by PET in healthy subjects. Hum Brain Mapp 30:2558–2570
Yanai K, Son LZ, Endou M, Sakurai E, Nakagawasai O, Tadano T, Kisara K, Inoue I, Watanabe T, Watanabe T (1998) Behavioral characterization and amounts of brain monoamines and their metabolites in mice lacking histamine H1 receptors. Neuroscience 87:479–487
Yen CY, Stanger RL, Millman N (1959) Ataractic suppression of isolation-induced aggressive behavior. Arch Int Pharmacodyn Thér 123:179–185
Young KA, Berry ML, Mahaffey CL, Saionz JR, Hawes NL, Chang B, Zheng QY, Smith RS, Bronson RT, Nelson RJ, Simpson EM (2002) Fierce: a new mouse deletion of Nr2e1; violent behaviour and ocular abnormalities are background-dependent. Behav Brain Res 132:145–158
Zarcone JR, Hellings JA, Crandall K, Reese RM, Marquis J, Fleming K, Shores R, Williams D, Schroeder SR (2001) Effects of risperidone on aberrant behavior of persons with developmental disabilities: I. A double-blind crossover study using multiple measures. Am J Ment Retard 106:525–538
Zeichner A, Pihl RO (1979) Effects of alcohol and behavior contingencies on human-aggression. J Abnorm Psychol 88:153–160
Zhuang X, Gross C, Santarelli L, Compan V, Trillat AC, Hen R (1999) Altered emotional states in knockout mice lacking 5-HT1A or 5-HT1B receptors. Neuropsychopharmacology 21:S52–S60
Zitzman D, DeBold JF, Miczek KA (2005) Positive modulation of the GABAA receptor heightens aggression in ovariectomized, nulliparous female mice. Program No. 76.15. 2005 Neuroscience Meeting Planner. Washington, DC: Society for Neuroscience. Online
Zouk H, McGirr A, Lebel V, Benkelfat C, Rouleau G, Turecki G (2007) The effect of genetic variation of the serotonin 1B receptor gene on impulsive aggressive Behavior and suicide. Am J Med Genet B Neuropsychiatr Genet 144B:996–1002
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Takahashi, A., Quadros, I.M., de Almeida, R.M.M. et al. Brain serotonin receptors and transporters: initiation vs. termination of escalated aggression. Psychopharmacology 213, 183–212 (2011). https://doi.org/10.1007/s00213-010-2000-y
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00213-010-2000-y